1. Field Of The Invention
The invention relates to a new process for the production of S-(+)-2,2-dimethylcyclopropanecarboxamide with new microorganisms suitable for the process. These microorganisms have been transformed with a new gene, which produces a stereospecific hydrolase, and thus is capable of biotransforming the R-(-)-isomer in racemic R,S-(.+-.)-2,2-dimethylcyclopropanecarboxamide into the corresponding acid, and optically active S-(+)-2,2-dimethylcyclopropanecarboxamide results.
2. Background Art
Hereinafter, 2,2-dimethylcyclopropanecarboxamide may be abbreviated 2,2-DMCPCA and 2,2-dimethylcyclopropanecarboxylic acid may be abbreviated 2,2-DMCPCS.
Optically pure S-(+)-2,2-DMCPCA is used as the initial material for the production of the dehydropeptidase inhibitor cilastatin, which is administered in therapy together with penem or carbapenem antibiotics, to prevent inactivation of the antibiotics by a renal dehydropeptidase in the kidneys (see European Published Patent Application No. 048301).
Examples of microorganisms which produce a stereospecific hydrolase for the R-(-)-2,2-DMCPCA are microorganisms of the species Comamonas acidovorans A:18 (DSM No. 6315), Bacterium sp. VIII:II (DSM No. 6316), Pseudomonas sp. NSAK:42 (DSM No. 6433) and Comamonas acidovorans TG 308 (DSM No. 6552) as well as their descendants and mutants. These microorganisms have already been described in detail in European Published Patent Application No. 92103780.0 (and in copending U.S. Ser. No. 845,034, filed on Mar. 3, 1992).